Li Bohai, Kwok Lai-Yu, Wang Dandan, Li Lu, Guo Shuai, Chen Yongfu
Key Laboratory of Dairy Biotechnology and Engineering, Ministry of Education, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China.
Inner Mongolia Key Laboratory of Dairy Biotechnology and Engineering, Inner Mongolia Agricultural University, Hohhot, Inner Mongolia, China.
Front Pharmacol. 2023 Jan 26;14:1047863. doi: 10.3389/fphar.2023.1047863. eCollection 2023.
Many drugs have been shown to be metabolized by the human gut microbiome, but probiotic-driven drug-metabolizing capacity is rarely explored. Here, we developed an integrated metabolomics, culturomics, and bionics framework for systematically studying probiotics-driven drug metabolism. We discovered that 75% (27/36 of the assayed drugs) were metabolized by five selected probiotics, and drugs containing nitro or azo groups were more readily metabolized. As proof-of-principle experiments, we showed that Zhang (LCZ) could metabolize racecadotril to its active products, S-acetylthiorphan and thiorphan, in monoculture, in a near-real simulated human digestion system, and in an fecal co-culture system. However, a personalized effect was observed in the racecadotril-metabolizing activity of Zhang, depending on the individual's host gut microbiome composition. Based on data generated by our workflow, we proposed a possible mechanism of interactions among Zhang, racecadotril, and host gut microbiome, providing practical guidance for probiotic-drug co-treatment and novel insights into precision probiotics.
许多药物已被证明可由人体肠道微生物群代谢，但益生菌驱动的药物代谢能力很少被研究。在此，我们开发了一个综合代谢组学、培养组学和仿生学的框架，用于系统地研究益生菌驱动的药物代谢。我们发现，75%（36种被测药物中的27种）被五种选定的益生菌代谢，含硝基或偶氮基团的药物更容易被代谢。作为原理验证实验，我们表明，在单培养、近真实模拟人体消化系统和粪便共培养系统中，张（LCZ）可将消旋卡多曲代谢为其活性产物S-乙酰硫辛酸和硫辛酸。然而，在张的消旋卡多曲代谢活性中观察到个性化效应，这取决于个体的宿主肠道微生物群组成。基于我们工作流程产生的数据，我们提出了张、消旋卡多曲和宿主肠道微生物群之间相互作用的可能机制，为益生菌-药物联合治疗提供了实际指导，并为精准益生菌提供了新的见解。
